Unseen toxins: Exploring the human health consequences of micro and nanoplastics

Abstract

Micro and nanoplastics (MNPs) contamination constitute a pressing global issue with considerable ramifications for human health. Particles originating from the decomposition of plastic waste permeate ecosystems and disturb biological systems, especially the gastrointestinal (GI) tract. MNPs compromise the intestinal barrier, provoke oxidative stress, inflammation, and immunological dysfunction, and modify gut microbiota, which is associated with metabolic problems, inflammatory bowel disease (IBD), and colorectal cancer. MNPs traverse biological barriers beyond the gastrointestinal system, including the blood-brain barrier, colonic mucus layer, and placental barrier, resulting in accumulation in essential organs such as the liver, kidneys, and brain. This results in inflammatory damage, metabolic abnormalities, and oxidative stress, specifically affecting liver disease due to microbiota metabolite alteration and nephrotoxicity in the kidneys. Airborne MNPs pose an additional risk to respiratory health, aggravating ailments such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. At-risk groups, such as pregnant women, newborns, and the elderly, encounter increased dangers, as MNPs traverse the placental barrier and may induce neurological and intergenerational health consequences. These particles function as vectors for environmental pollutants, exacerbating their cardiovascular and neurological effects. Addressing the long-term consequences of MNP exposure necessitates interdisciplinary collaboration to enhance comprehension and alleviate their growing risk to human health.

Graphical Abstract

Highlights

• •Micro and nanoplastics circulate through the bloodstream and build up in the body.
• •Oxidative stress, protein dysregulation, and lysosomal damage are key pathways.
• •Long term MNP exposure possesses the carcinogenicity potential.
• •Disruptions on the gut-brain axis led to neurogenic disorders.
• •Smaller MNPs pose a greater health risk by more easily infiltrating tissues and cells.

1. Introduction

Plastics represent a critical global environmental challenge. As synthetic polymers, they are used daily for their low cost, durability, and versatile applications. Since their widespread adoption in the 1950s, plastic production has risen dramatically, reaching 400 million metric tons per year by 2022 [1]. However, this remarkable growth in plastic production has come with a steep environmental price. Plastic pollution now ranks among the most urgent challenges of our time, infiltrating every corner of the planet. At the heart of this crisis lie MNPs the smallest fragments of plastic that are invisible to the naked eye yet ubiquitous in the environment. Microplastics (MPs), defined as plastic particles with size from 1 µm to 5 mm, degrade over time to form nanoplastics (NPs), an even more concerning byproduct. NPs, are characterized by their size of less than 1 µm. Both pose unique environmental and health challenges due to their minute scale and increased potential for bioavailability [2], [3]. These microscopic particles, whether formed from the breakdown of larger plastics or intentionally manufactured, are pervasive and persistent. MNPs permeate many facets of our environment, including the soil, water, and air. Their distribution encompasses isolated high-altitude plateaus and the ocean's deepest regions, demonstrating their concerning capacity for global dispersion [4]. Their omnipresence highlights a global crisis that demands urgent attention.

Among the most alarming pathways of MNP contamination is the atmosphere. Airborne MNPs carried by winds over vast distances, are not merely global pollutants but personal ones. With every breath, humans potentially introduce these particles into their respiratory systems, raising critical questions about their long-term health impacts [5], [6]. Urban environments and indoor spaces, act as hotspots for exposure, with synthetic textiles, industrial emissions, and household activities contributing to an invisible storm of plastic particles. This has revealed alarmingly high exposure rates in such settings, underscoring the need to address airborne plastic pollution as a priority [7].

Agricultural soils are inundated with MNPs through fertilizers, compost, and irrigation, altering soil properties and potentially compromising food security [8]. Oceans and freshwater systems have become reservoirs for these particles, with MNPs detected in drinking water, defying treatment processes and raising concerns about chronic ingestion [9], [10], [11]. Marine ecosystems, however, endure most MNP contamination. These particles accumulate in marine organisms across trophic levels through bioaccumulation and biomagnification [12], [13]. Bioaccumulation occurs when organisms absorb MNPs faster than they can eliminate them, leading to increased concentrations in tissues [14]. Biomagnification amplifies this effect as predators consume contaminated prey, resulting in higher MNP levels at each step of the food chain.

Plankton, which form the base of the marine food web, are often exposed and ingest smaller-sized MNPs than those found in surface waters. [15]. It is noted that factors such as swimming speed, perception distance, and MP concentration, increase the likelihood of plankton ingesting these pollutants, especially during windy conditions. This contamination cascades upward, impacting secondary consumers such as copepods, chaetognaths, and luciferids [16]. This exposed the tropic transfer of MNPs to multiple organisms in marine environment. Further, Costa et al. have detected MPs in the gastrointestinal tracts of 29 fish species along the Machado River in Brazil, with polyurethane identified as a particularly harmful polymer [17]. Similarly, studies conducted by Hidayati et al. in Central Java and Zeghdani et al. in Algeria highlight the widespread presence of microplastics in commercially important fish species, underscoring the global scale of this environmental crisis [18], [19].

Shellfish, which often contain even higher levels of MPs than fish, are major contributors to human ingestion. The average person is estimated to consume approximately 781 MP particles annually through fish and 2,809 particles through shellfish. The abundance of MPs in shellfish ranges from 0.75 ± 0.12 to 9.7 ± 0.28 particles/g, highlighting the role of these organisms as key vectors for MNP transfer in marine ecosystems [20]. Beyond fish and shellfish, seabirds also ingest MNPs, contaminating their livers with hazardous chemicals such as bromodiphenyl ethers, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organochlorine pesticides [21]. In tuna and their prey, MPs have been detected in 100 % of examined tuna and 70 % of their prey, with cephalopods and Bramidae fish among the most contaminated [22]. Even baleen whales, which feed at depths of 50–250 m, are highly vulnerable, with krill-eating species consuming up to 10 million MNP daily [23]. MNPs were found in 80 % of bivalve samples from Qingdao, China, with species and region-specific differences. Predominantly microfibers, MPs included polyvinyl chloride and rayon. Clams reflected sediment pollution, while mussels indicated waterborne MNPs. Bivalves serve as bioindicators of MP pollution and potential transporters to humans, warranting further attention [24], [25], [26], [27].

The persistent nature of MNPs extends to marine mammals, including dolphins, seals, sea urchins, and sea lions, with polyethylene and fibers being the most prevalent types [28], [29], [30]. Long-term exposure evidenced by decades of collected samples demonstrates the enduring and hazardous nature of this pollution. MNPs in lipid-rich tissues may exacerbate the toxic effects of plastic pollution, further underscoring the urgency of mitigation efforts [31].

Despite their ubiquity, the health risks posed by MNPs remain poorly understood. These particle’s small size and persistent nature enable them to penetrate cellular barriers, potentially triggering inflammation, oxidative stress, and apoptosis [32]. Moreover, their interactions with other pollutants may magnify their toxicological impacts. For instance, MNPs are known to adsorb and transport hazardous chemicals, acting as vectors for pollutants that may further harm biological systems [33], [34].

This review explores the potential pathways through which MNPs may exert adverse effects on human health. By synthesizing current research on their exposure, and biological interactions, it aims to illuminate the hidden dangers of these microscopic pollutants. Addressing this emerging health crisis requires interdisciplinary efforts to understand MNPs impacts fully and to develop effective strategies for mitigation and prevention.

2. MNPs production and their toxic nature

Environmental stressors play a crucial role in facilitating MNPs formation. UV radiation, saline infiltration, and temperature fluctuations lead to physical changes in plastic materials, such as increased surface roughness and brittleness, making them more susceptible to fragmentation [35]. Photochemical reactions initiated by UV radiation further break down the polymer matrix, reducing its molecular weight and releasing dissolved organic carbon and additives [36]. Mechanical abrasion, driven by activities such as wave motion, sediment contact, and everyday actions like opening bottles, accelerates microplastic release, particularly in degraded plastics, which shed more particles under stress than new materials [37]. This ongoing degradation, coupled with the wear and tear of polymeric materials, continues to contribute to both global and human accumulation of MNPs as illustrated in Fig. 1.

Fig. 1.

Biodiversity & Environmental Accumulation of MNPs. This figure illustrates MNP fragmentation and subsequent accumulation within various biological entities.

Fibrous MPs are a distinctive category of MPs, defined by their small size, flexibility, and primary release through textile washing [38]. These fibers include both natural materials such as cotton and asbestos and synthetic fibers, including polyester, polypropylene, and polyacrylic. Synthetic fibers, often originating as secondary MNPs, represent a major source of fibre type MP pollution, with up to 70 % of fibers entering wastewater treatment plants stemming from textile washing [39]. These fibers often carry harmful chemicals such as dyes, antimicrobial agents, and water repellents, which can affect both human health and the environment. Natural fibers, like cotton, although biodegradable, also release harmful fibers during washing. Other major sources of microfibers include cigarette filters, fishing gear, and personal care products [40]. These fibers contain various toxic chemicals, such as polycyclic aromatic hydrocarbons and metals, which pose additional environmental risks. However, many of these fibers escape water treatment, contaminating freshwater and marine environments, soils, and even polar regions.The extent of this pollution is largely driven by the properties of synthetic fibers, which make up approximately 35% of global marine MNPs contamination [41]. Meanwhile, emerging biopolymer-based fibers, such as polylactic acid, present biodegradable alternatives, but their environmental impact remains minimal at present [42]. Beyond the fibers themselves, textile manufacturers often enhance fabric performance using polymeric coatings to improve water repellence, durability, breathability, and UV resistance. However, these coatings degrade under mechanical stress, UV exposure, and chemical interactions, contributing to the release of MNPs during washing and environmental wear. Common coatings like polytetrafluoroethylene and polyethylene generate millions of MNPs [43], and prolonged UV exposure accelerates the breakdown of coatings such as melamine and polyvinylchloride [44], exacerbating the MNPs pollution cycle. Some of these additives, such as bisphenol A and phthalates, are known endocrine disruptors that can cause harm to human and environmental health [45]. Over 13,000 chemicals are used in plastics globally, with many considered potentially toxic, but their full toxicological impact is still not well understood [46]. Common toxic chemicals found in MNPs, including bisphenol A, phthalates, and perfluorooctanesulfonic acid, can cause developmental, reproductive, and neuroendocrine system changes in humans and other species [47].

Mitigation strategies focus on reducing the release of polymeric fragments through innovative treatments and coatings. Advances include chemical treatments using acrylic, polyurethane, and silicon emulsions to enhance coating adhesion and minimize fiber shedding during washing [48]. Promising technologies, such as electrofluidodynamic coatings, have shown considerable success polyethylene carbonate and glycidyl methacrylate coated polyamide fabrics, for example, have reduced fiber loss by up to 90 % [49]. However, even durable coatings are not immune to over time, maintaining the ongoing release of MNPs into the environment.

Furthermore, everyday mechanical forces ranging from industrial processes and recycling operations to daily activities significantly contribute to MNPs pollution. For instance, trail running can release up to 0.9 MNPs per linear meter from shoe outsoles, and hot water exposure can increase particle release by 10 % [50]. Melamine cleaning sponges ("magic erasers") release Fibrous MNPs during use, with up to 6.5 million particles/g emitted. These fibers (10–405 μm) are composed of poly(melamine-formaldehyde) and form due to friction-induced polymer decomposition. MNPs generation increases with sponge density and surface roughness, contributing to an estimated global emission of 4.9 trillion MNPs annually. From this Su et al., identify melamine sponges as a significant and overlooked source of MNP pollution, raising concerns about environmental and health risks [51]. Long-term exposure to environmental stressors, such as during waste management or the wear of polymer composites in infrastructure, further exacerbates the contamination [52]. To effectively address the growing issue, comprehensive pollution control strategies are essential. These must involve regulation of industrial and consumer activities to reduce both acute and chronic exposure risks, ensuring the protection of environmental and public health. Interestingly, Honey samples from Turkiye were analyzed for MNPs contamination, revealing an average of 314 ± 353 particles/kg across 32 samples. MPs included four polymers Ethylene-Vinyl Acetate, polyethylene, polypropylene, nylon-6, two shapes such as fibers, fragments, and six colors. Daily intake via honey consumption was estimated at 1.20 particles/day for monofloral and 0.85 particles/day for multifloral honey. Polymer hazard and MNPs load indices averaged 16.7 ± 16 and 6.70 ± 1.0, respectively. The findings confirm honey contamination with MNPs, highlighting the need for improved production processes and strategies to mitigate risks to human health [53]. MNPs were also detected in 17 commercial salt brands from 8 countries. MNPs were found in all but one brand, with concentrations ranging from 1 to 10 particles/kg. Of 72 particles extracted, 41.6 % were plastics primarily polypropylene & polyethylene, with fragments as the dominant form (63.8 %). The average particle size was 515 ± 171 μm. Annual intake was estimated at a maximum of 37 particles per individual, posing negligible health risks. Improved methods to isolate smaller particles less than 149 μm are needed to fully assess the potential health impacts of salt consumption [54].

These findings underscore the pervasive nature of fibrous MNPs pollution and its potential long-term effects on ecosystems and human health as identified in Fig. 2. As fibers and particles infiltrate air, water, and soil, their cumulative impact raises concerns about biodiversity, food security, and public health risks. It is essential to prioritize sustainable practices in textile production and disposal while advancing research into the ecological and physiological effects of these pollutants. The urgent need for risk assessments and targeted mitigation strategies cannot be overstated, as the consequences of inaction will likely reverberate across generations.

Fig. 2.

Trends and Correlations in MNPs Research (2020-2024). This figure, generated using VOS viewer software with data retrieved from PubMed, illustrates the network of studies conducted from 2020 to 2024 on MNPs and their adverse effects on human health. The visual mapping underscores the rising concern and research focus in this field, reflecting the growing awareness and urgency to address potential health risks associated with these contaminants.

3. MNPs transportation inside of human body

MNPs enter the human body through multiple exposure routes, primarily via inhalation and ingestion, and their widespread presence raises pressing health concerns (Fig. 3). Inhalation, one of the major pathways, allows MNPs to deposit in the respiratory system. Studies have found fibers composed of polycarbonate, polyvinylchloride, and polyamide in human sputum and nasal lavage fluids [55], [56]. Intriguingly, individuals with lung diseases exhibited a broader spectrum of MNPs, such as polyurethane and poly ethylene terephthalate, which underscores the potential for compromised respiratory systems to retain and interact with diverse pollutants [57]. Analysis of bronchoalveolar lavage fluid (BALF) further revealed that MNPs penetrate deep into the lower respiratory tract, averaging 9.18 ± 2.45 particles/100 mL, primarily in microfiber form [58]. This highlights a critical point that inhaled MNPs not only cross respiratory barriers but may also disseminate throughout the body, posing risks such as chronic inflammation and progressive lung damage.

Fig. 3.

MNP exposure & accumulation in various human organs. This image illustrates the potential transfer of MNPs within the human organism, based on insights gleaned from previous studies.

Ingestion is another significant route, with MNPs accumulating in the gastrointestinal tract, particularly in the intestines. Alarmingly, non-digestive organs such as the liver and pancreas also show evidence of MNP presence, suggesting systemic distribution [59], [60]. Stool analyses consistently demonstrate MNP contamination, with samples containing 3.5 particles/g [61]. Elevated microplastic levels in feces have been linked to diseases such as inflammatory bowel disease, which hints at their possible role in disease exacerbation [62]. This raises an important question, could dietary habits and frequent consumption of plastic-contaminated food and water be silently contributing to the rising incidence of gastrointestinal disorders? Although ingested MNPs are excreted [63], the annual human intake is estimated at up to 90,000 particles/day through water, food, and packaging materials. Seafood, bottled water, and plastic containers are identified as primary sources, pointing to the pervasive nature of plastic contamination in daily life [64]. This statistic emphasizes the pressing need for intervention at both industrial and consumer levels to reduce MNPs contamination at its source.

Dermal exposure to MNPs is an area of growing scientific investigation. Although research in this field is still evolving, studies have confirmed the presence of MNPs in cosmetic products [65], [66], [67]. A comprehensive study by the Plastic Soup Foundation found that 9 out of 10 well-known cosmetic products contain MNPs, including various synthetic polymers in solid, liquid, semi-liquid, or water-soluble forms, as well as NPs and biodegradable plastics [68]. The ability of MNPs to penetrate human skin remains debated.

However, Song et al., demonstrated in a study using 3D skin models, mouse dorsal skin, and human abdominal skin models that polystyrene MNPs can penetrate the skin. The same study also found that these particles trigger an inflammatory response in a dose-dependent manner, raising concerns about the potential health impacts of dermal exposure to MNPs [69]. Although real-world exposure conditions may differ from controlled laboratory settings, these findings highlight the importance of investigating the potential adverse effects of MNPs on human skin. Shockingly, MNPs were detected in the vitreous humor of 49 patients with ocular diseases, with 1745 particles identified with size less than 50 μm. Nylon 66 was the most abundant polymer. They were linked to intraocular pressure and opacities, with retinopathy patients at higher risk. This highlights MNPs infiltration in the eye and calls for further study of their health effects [70]. Plastic particles have also been detected in the human bloodstream, with common polymers like poly ethylene terephthalate and styrene-based plastics found in blood samples. Leslie et al., reported an average concentration of 1.6 µg/mL of plastic particles in human blood, revealing that MNPs can indeed enter the circulatory system [71]. Additionally, polystyrene beads as small as 240 nm have been shown to pass through the placenta, with smaller particles being transported more rapidly [72]. Their presence in vascular tissues, including saphenous veins and bone marrow, confirms the ability of MNPs to cross biological barriers and potentially influence vascular health [73], [74], [75]. Similarly, their detection in urine suggests continuous systemic exposure. These findings raise an important question how does chronic exposure to these particles influence circulatory and renal function over time?

The reproductive system is also subject to MNP accumulation. Studies have identified MNPs in male reproductive tissues, such as the testes, semen, and prostate, and in female tissues, including the endometrium, myometrium, and placenta [76], [77], [78], [79], [80]. Notably, placental MNPs composed of polypropylene, polyvinyl chloride, and polyamide were found on both the maternal and fetal sides, with particles small enough to facilitate fetal transmission [81]. This revelation is particularly troubling, as it suggests that exposure to MNPs begins in utero, potentially impacting fetal development and long-term health outcomes. Adding to the concerns, MNPs have been detected in breast milk, a critical source of infant nutrition. Studies have identified MNPs in 26 out of 34 milk samples, with dimensions ranging from 2 to 12 µm. The predominant materials included polyethylene, polyvinylchloride, and polypropylene, with polyurethane accounting for over half of the particles in some cases [82].

While no significant link between plastic use and MNPs prevalence in breast milk was observed, this finding emphasizes the omnipresence of MNPs and their potential early-life exposure risks. The widespread presence of MNPs across various tissues and fluids including blood, reproductive tissues, skin, and the gastrointestinal tract underscores their pervasive nature and associated health risks. Chronic exposure has been linked to inflammation, cytotoxicity, and potentially long-term effects such as organ dysfunction and developmental abnormalities. This mounting evidence highlights a critical gap in understanding What are the cumulative effects of prolonged exposure to MNPs on human health, and how can we mitigate these risks effectively. To address these challenges, future research must focus on developing comprehensive risk assessments, identifying key exposure sources, and exploring innovative strategies to minimize human interaction with MNPs. With increasing evidence of their systemic impact, reducing MNP exposure is imperative to safeguard both current and future generations. The ubiquity of MNPs serves as a stark reminder of the urgent need for a global effort to curb plastic pollution and mitigate its far-reaching consequences.

4. Potential health impact pathways of MNPs on human health

The widespread occurrence of MNPs in the environment has elicited increasing apprehension regarding their possible effects on human health. These minuscule plastic particles, derived from diverse sources such as industrial activities, textiles, and decomposed trash, can enter the human body via inhalation, ingestion, and cutaneous exposure. Upon entry, MNPs engage with biological systems, traversing physical and physiological barriers to accumulate in vital organs, including the lungs, liver, gastrointestinal tract, and reproductive tissues. This accumulation of MNPs in human health was proven by many research findings that are included in Table 1. Recent findings underscore their capacity to provoke localized inflammation, oxidative stress, and cytotoxic effects, which may result in prolonged health repercussions as mentioned in Fig. 4. As research advances in elucidating the complex mechanisms by which MNPs influence human health, comprehending these processes is essential for evaluating risks.

Table 1.

Research Summary on micro and nanoplastics accumulation across human samples.

Sample	No. of samples	Concentration of MNPs	Size of MNPs	Types	Ref.
Stomach	26	9.4 ± 10.4 particles/individual	Fibers - 1196.6 ± 907.1 µm, Films - 635.6 ± 310.8 µm Fragments - 330.4 ± 261.4 µm	PE, PP, PMMA, Polyamide, PET & Polyester	[60]
Colorectal cancer tissue	11	331 MPs/ individual or 28.1–15.4 particles/g tissue	0.8–1.6 mm	PC, PA, PP	[189]
Liver	11	0–13 particles per sample or 3.2 particles/g tissue	4–30 μm	PS, PVC, PET, PMMA, POM, PP	[106]
Placenta	62	6.5–685 µg MNPs/gram	>1 μm	PE, PVC, Nylon, PET, PP, PS, Rayon, PMPS	[190]
Placenta	17	149	20.34–307.24 μm	PVC, PP, PBS, PET, PC, PS, PA, PE, PSF	[191]
Sputum	22	18.75–91.75 particles/10 mL	20–500 μm	PU, PES, CPE & AV	[55]
Blood	22	1.6 µg/mL	≥ 700 nm	PET, PE, & PP	[71]
Thrombi	26	87 particles	2.1–26.0 l µm	LDPE, Synthetic materials	[192]
Vein	5	20 particles or 14.99 ± 17.18 microplastic/g of tissue	16–1074 μm	Alkyd Resin, Poly (vinyl propionate), Nylon ethylene-vinyl acetate, nylon-EVA, tie layer	[193]
Carotid artery plague	304	21.7 ± 24.5 μg/mg	< 1 μm	PE, PVC	[194]
Heart tissues	15	NA	< 469 μm	PMMA, PVC, PE, PET, PA, PC, PS, PP & PU	[73]
Human blood	36	4.2 MPs/mL	< 100	PS, PP	[195]
Human semen	10	16 Particles	2–6 μm	PP, PE, PET, PS, PVC, PC, & POM	[196]
Breast milk	34	58 in total	2–12 μm	PE, PVC, PP, CPE, PVOH, PEVA, PEMA, ABS, PES, PA, PC, PS, NC	[82]
Breast milk	7	20.2 MPs/g	> 20 μm	PA, PU, PE, PET, PP, PVC, POM, EVA, PTFE, CPE, Polybutadiene, PS, PMMA, PLA, Polysulfones	[197]
Semen	25	0.23 ± 0.45 MPs/mL	21.76–286.71 μm	PVC, PE, PA, PP, PS, PET	[76]
Human vitreous humor	49	8543 particles in total	< 50 μm	Nylon 66, PVC, & PS	[70]
Bone marrow	16	51.29 µg/g	< 100 μm	PE, PS, PVC, PP & PA-66	[198]
Bronchioalveolar lavage	10	0.14–12.8 MPs/100 mL	10–300 μm	NA	[199]
Skin	2000	Face = 4265 MPs Hair = 7462 MPs Hand = 4051 MPs	100–500 μm	PE, PET, PS, PVC	[200]
Saliva	2000	645 MPs	100–500 μm	PE, PET, PS, PVC	[200]
Human endometrium	20	21 MPs/100 mg	20–500 μm	ACR PE PET PP PS PU PVC BR CPE EAA FR EVA PER	[78]
Uterine fibroids & Myometrium	48	1.5 ± 1.17 MPs/g	2.79–22.79 μm	PE, PP, PEVA, PE-co-PP, ABS	[79]
Human lower limb joints	45	1.16–10.77 MPs/g	50.01 ± 22.07 µm	PET, PE, rayon, PES, PP, PA, PVC, PS, and PC	[201]
Nasal lavage fluid	113	41.24 ± 1.73 MPs/g	100–200 µm	PP, PC, PE, PET & PA	[56]
Penile tissue	6	46 in total	20–500 µm	PET, PP, PMMA, PS, PVC, PTFE, PU,	[202]
Kidney	66	26 in total	1–29 μm	PE, PS, Styrene isoprene	[203]
Urine	66	26	3 and 13 μm	PE, PS, Styrene isoprene	[203]
Feces	12	26.6 particles/g	NA	PA, PU, PE, PET, PP, PVC, POM, EVA, PTFE, CPE, Polybutadiene, PS, PMMA, PLA, Polysulfones	[197]

Abbreviations: PE - Polyethylene; PP - Polypropylene; PMMA - Polymethyl methacrylate; PA - Polyamide; PET - Polyethylene terephthalate; PES - Polyester; PC - Polycarbonate; PS - Polystyrene; PVC - Polyvinyl chloride; POM - Polyoxymethylene; Nylon - Generic term for polyamide fibers; Rayon - Regenerated cellulose fiber; PMPS - Poly(methylphenylsiloxane); PBS - Polybutylene succinate; PSF - Polysulfone; PU - Polyurethane; CPE - Chlorinated polyethylene; AV - Not a common polymer abbreviation (please clarify); LDPE - Low-density polyethylene; Synthetic materials - Broad category, not an abbreviation; Alkyd Resin - Polymer derived from polyesters; Poly (vinyl propionate) - Polymer of vinyl propionate; Nylon-EVA - Copolymer of nylon and ethylene-vinyl acetate; Tie layer - Adhesive layer used in multilayer materials; PEVA - Polyethylene vinyl acetate; PVOH - Polyvinyl alcohol; PEMA - Poly(ethyl methacrylate); ABS - Acrylonitrile butadiene styrene; NC - Nitrocellulose; EVA - Ethylene vinyl acetate; PTFE - Polytetrafluoroethylene; Polybutadiene - Synthetic rubber polymer; PLA - Polylactic acid; Polysulfones - High-performance thermoplastics; PA-66 - Nylon 66, a specific type of polyamide; BR - Butadiene rubber; EAA - Ethylene acrylic acid; FR - Flame retardant; PER - Perfluorinated polymers; PE-co-PP - Polyethylene-co-polypropylene; Styrene isoprene - Copolymer of styrene and isoprene.

Fig. 4.

Mechanisms of MNP cellular toxicity and their adverse effects. The figure illustrates how micro and nanoplastics (MNPs) induce cellular toxicity by causing cell death, triggering inflammation through immune cell damage, generating reactive oxygen species (ROS) that damage mitochondria, disrupting genes, dysregulating proteins, and accumulating in microbiota. They also compromise tissue and blood barriers through mechanical disruption. These processes result in adverse effects such as chronic inflammation, tumor formation, carcinogenicity, and genomic alterations.

4.1. Gastrointestinal system

The gastrointestinal tract stands as a frontline battleground for MNPs, given their pervasive presence in our food web [60]. These tiny intruders do not merely pass through but their effects are dictated by their size, surface features, and concentration, making them far from innocuous (Fig. 6a). More concerning is those measuring 50–100 nm slip into intestinal villi, while larger ones such as 300 nm to 3 µm exploit Peyer’s patches to gain entry [83]. The smallest particles, less than 10 µm, penetrate the intestinal barrier, opening a direct route to systemic exposure. Once inside body, their journey becomes even more sinister, particles over 144 nm take up residence in the liver, while those under 10 nm are rapidly filtered by the kidneys [84].

Fig. 6.

Potential mechanistic pathway of MNP toxicity in human organs. The potential toxicity mechanism of MNP in a) the Gastrointestinal tract, b) the Liver, c) the Kidney, d) the Male and female reproductive system, e) the Lungs, f) Blood vesicles, g) the Heart, and h) the Brain are illustrated here.

MNPs possess chemical guile as well positively charged particles are more toxic. Their systemic absorption undermines the gastrointestinal tract’s defenses beginning with the mucus layer, an essential barrier. These particles deplete goblet cells, block mucin secretion, and suppress genes critical for mucus production, such as Muc1, Muc2, and Klf4 [85], [86]. As the mucus shield erodes, the underlying epithelial cells are left vulnerable to harmful substances. Simultaneously, MNPs weaken tight junction proteins like ZO-1, claudin-1, and occludin, compromising the gut’s mechanical barrier a flaw that becomes glaring in conditions like colitis [87], [88].

This disruption fuels a cascade of inflammation. MNPs stimulate the release of inflammatory messengers, such as interleukins (IL-1α, IL-1β, IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) [89], [90]. These cytokines activate potent signaling pathways like NF-κB and NLRP3, exacerbating intestinal inflammation, systemic toxicity, and even liver damage. Beyond sparking inflammation, MNPs suppress the immune system, hindering T-cell activation and reducing secretory immunoglobulin A (sIgA), which leaves the body prone to infections and systemic repercussions [91]. The plot thickens as MNPs wreak havoc on the gut microbiota a cornerstone of gastrointestinal health. Research shows MNPs can either disrupt the balance of dominant bacterial groups, like Firmicutes and Bacteroides or trigger dysbiosis, promoting the growth of harmful bacteria like Enterobacteriaceae [91]. This microbial upheaval worsens oxidative stress, a key player in cellular damage. By elevating reactive oxygen species (ROS) and depleting antioxidants like catalase and glutathione, MNPs set the stage for oxidative stress, which further disrupts tight junctions and triggers cell death in intestinal epithelial cells [92].

Adding to this turmoil, MNPs derail the body’s metabolic machinery, impairing pathways for amino acid, pyruvate, and fatty acid metabolism potentially paving the way for obesity and diabetes. They also interfere with ion transport, disrupting channels like CFTR and NKCC1, which leads to imbalances in water and ion movement [93]. The suggested cellular toxicity mechanisms of MNP in gastrointestinal cells are illustrated in Fig. 5. Prolonged MNP exposure is not just disruptive, it is deadly. Cells succumb to apoptosis, driven by oxidative stress, or autophagy, marked by elevated LC3II/I and p62 proteins [94]. Inflammatory necroptosis, involving RIPK1 and MLKL, leaves intestinal tissue in disrepair. Even colon function deteriorates, as MNPs downregulate muscarinic acetylcholine receptors (M2 and M3), essential for water absorption and ion balance. The result is a cascade of delayed fecal transit, inflammation, and systemic damage [95].

Fig. 5.

Proposed signalling pathways- a) The signal pathway illustrates how MNPs are triggered when they enter cells. Micro and nanoplastics (MNPs) enter cellular tissues through endocytosis and direct penetration. Ligands interact with receptors such as Toll-like receptor 4 (TLR4) and muscarinic acetylcholine receptors (mAChRs), triggering downstream signaling pathways that alter DNA transcription. Reactive oxygen species (ROS) play a key role by directly activating NLRP3 inflammasomes and nuclear factor kappa B (NF-κB), with NF-κB being pivotal in mediating these signalling cascades. b) MNP-induced death of rodent intestinal cells includes various forms of cell death such as apoptosis, which can be triggered by internal or external signals, autophagy-dependent cell death, and necroptosis. Key proteins involved are B-cell lymphoma-2 (Bcl-2), which prevents cell death, and Bcl-2-associated X protein (Bax), which promotes it. Microtubule-associated protein 1 light chain 3 (LC3) is associated with autophagy, while lysosome-associated membrane glycoprotein 2 (LAMP) plays a role in lysosome function. Receptor-interacting serine/threonine-protein kinase (RIPK) and mixed linear kinase-like (MLKL) are critical in necroptosis, and fas-associating protein with a novel death domain (FADD) is involved in cell death signaling.

This alarming narrative of MNPs in the gastrointestinal tract underscores how their relentless assault through barrier disruption, inflammation, oxidative stress, and metabolic chaos poses a grave threat not only to digestive health but to overall systemic well-being.

4.2. Hepatic impairment

The gut-liver axis is a vital physiological connection that regulates signals between the gut and liver, shaped by nutritional, genetic, and environmental influences [96]. The portal vein, biliary tract, and systemic mediators link the gut to the liver, enabling the flow of nutrient-rich blood, signaling molecules, and gut-derived antigens [96]. An intact intestinal barrier inhibits the dissemination of infections and poisons, preserving homeostasis. Nonetheless, elements like as inflammation, dysbiosis, high-fat diets, chronic alcohol consumption, and extended antibiotic usage compromise the barrier (Fig. 6b) [97], [98]. This permits germs and detrimental metabolites to infiltrate the liver, inciting inflammation, and hepatic damage [99]. Dysbiosis, frequently intensified by MNPs, has been associated with hepatic disorders including alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) [100], [101], [102]. MNPs elevate blood concentrations of lipopolysaccharides (LPS), activating inflammatory pathways detrimental to the liver [103]. They directly influence the gut-liver axis by modifying gut microbiota, compromising the intestinal barrier, and facilitating systemic inflammation. Research with animals, such as zebrafish and chickens, demonstrates that MNPs disrupt tight junction proteins in the colon, allowing detrimental bacteria and endotoxins to infiltrate the liver, resulting in hepatic metabolic disorders and inflammation [104], [105]. Probiotics, prebiotics, and synbiotics may alleviate MNP-induced harm by reestablishing gut microbial equilibrium and fortifying the intestinal barrier. No direct investigations have investigated the impact of MNPs on the human liver. However, MNPs have been identified in the liver tissues of both healthy persons and those with cirrhosis [106]. Research from animal and laboratory investigations underscores the hepatotoxic effects of MNPs. As well as they induce damage to hepatocytes by instigating structural abnormalities, including cellular swelling, vacuolation, and compromised cell connections. They disrupt lipid metabolism, leading to fatty liver and cholestasis, characterized by the accumulation of toxic bile acids that induce inflammation [99]. MNPs also provoke oxidative stress, affect energy metabolism, and compromise neuronal function. Furthermore, they influence triglyceride (TG) and bile acid (TBA) metabolism, aggravating hepatic dysfunction [107]. Types of MNP such as polystyrene, polyethylene, and polypropylene exhibit unique but intersecting toxicological effects. polystyrene MNPs penetrate hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells, resulting in cellular apoptosis and reactive oxygen species generation while diminishing detoxifying enzyme function [108]. Polyethylene MNPs diminish liver cell viability and cause DNA damage, whereas polypropylene MNPs instigate lipid peroxidation, DNA damage, and substantial metabolic alterations. Zebrafish subjected to polystyrene MNPs exhibited a significant rise in hepatic DNA damage [109]. Secondary MNPs interfere with iron homeostasis, exacerbating cellular damage by modifying iron storage and transport systems [110]. These findings highlight the necessity for additional investigation into MP-induced toxicity and methods to safeguard liver health.

4.3. Impacts on renal health

The impact of MP exposure on human renal health is inadequately investigated, primarily relying on findings from animal and in vitro research (Fig. 6c). Evidence indicates that MNPs cause histological and functional alterations in animal kidneys, prompting worries regarding potential consequences for humans [111]. Urinary excretion seems to serve as a mechanism for the removal of MNPs, as indicated by their presence in human urine [112]. Research on animals suggests that MNPs can access the proximal convoluted tubules through peritubular capillaries after traversing the glomerular tuft, however, the intact filtration barrier restricts their movement due to size constraints. Upon entering the tubules, MNPs are internalized by epithelial cells through endocytosis or macropinocytosis and are subsequently ejected [112], [113]. In vitro investigations reveal substantial cellular changes following MNP exposure. In HK-2 kidney cells, MPs augment mitochondrial ROS, enhance pro-apoptotic and inflammatory markers, and promote endoplasmic reticulum stress. These abnormalities impact essential signaling pathways, including the mitogen-activated protein kinase (MAPK) and protein kinase B cascades [114]. Likewise, HEK 293 cells subjected to 1 μm polystyrene MPs at a concentration of 5 μg/mL for a duration of up to 72 h demonstrated morphological alterations, diminished proliferation, and increased ROS levels [115]. Fluorescent polystyrene NPs (50 nm, 200 μg/mL for 24 h) further compromised microstructures in HK-2 cells and stimulated markers such as JNK1/2/3 and TNF-α. Animal studies validate these findings, demonstrating size-dependent toxicity and MNP buildup in the kidneys [116]. Meng et al., established that male mice subjected to polystyrene MNPs with size of 300 nm, 600 nm, 4 μm and 50 nm through drinking water exhibited weight reduction, heightened mortality, histological renal impairment, oxidative stress, inflammation, and modified lipid metabolism [117]. Increased MNP size resulted in heightened toxicity. Fluorescent polystyrene MNPs sizes 5 μm and 20 μm further validated bioaccumulation and metabolic disturbances in murine kidneys [118]. Additional studies underscore the systemic effects of MPs after oral ingestion. Kidney accumulation correlates with alterations in hematological markers and lipid metabolism. Evidence of maternal-fetal translocation MNPs seen in amniotic fluid and placenta raises apprehensions for fetal renal health [119]. In juvenile rats, oral exposure to MNP resulted in nephrotoxicity, evidenced by oxidative stress, histopathological damage, and increased indicators of renal injury such as blood urea nitrogen and serum creatinine levels [116]. MNPs further exacerbated cadmium-induced renal injury, indicating possible synergistic effects. Environmental and physiological factors may affect the nephrotoxicity of MNPs [120]. The concern here is chronic kidney disease may intensify intestinal MNP absorption due to impaired barrier integrity, heightening concerns for protracted exposure. Critical unresolved inquiries encompass the degree of MNP filtration by glomeruli, their influence on chronic kidney disease advancement, and the prospective burden on individuals receiving renal replacement therapy. Materials used with dialysis, such as catheters and dialyzers, may also contribute to MNP exposure, warranting additional research. Although MNPs have been identified in human kidneys and urine, the mechanisms of renal clearance and tubular secretion in the removal of MNPs are not well comprehended. The enduring effects of prolonged, low-dose exposure to MNPs remain ambiguous. Experimental models highlight the nephrotoxic and systemic effects of MNPs, emphasizing the critical necessity for thorough investigations to clarify their impact on renal health and overall human welfare.

4.4. Impacts on reproductive health

MNPs have infiltrated numerous human tissues, including the brain, blood, liver, lungs, placenta, testes, and cervical cancers, like intruders encroaching upon areas where they are unwelcome. Daily exposure to MNPs results in their buildup in vital organs like the reproductive system, significantly impacting its health (Fig. 6d).

In male reproductive systems, MNPs work as disruptive agents, impairing Sertoli and interstitial cells crucial for testicular function. These minuscule particles disrupt the blood testis barrier, inducing oxidative stress, diminishing enzyme activity, and inflicting structural damage to reproductive organs [121]. Research on rats exposed to polyethylene NPs indicates that these contaminants adversely affect sperm quality and testosterone secretion, compromising fertility [122]. Likewise, in female systems, MNPs disrupt ovarian function, comparable to a wrench obstructing the mechanisms of a sensitive apparatus. They diminish oocyte maturation and fertilization rates while elevating oxidative stress, mitochondrial malfunction, and apoptosis [123]. Hormonal imbalances intensify these disruptions, underscoring the susceptibility of the hypothalamic-pituitary-ovarian axis to these intrusions [124], [125]. The effects of MNPs reverberate over generations, akin to a stone thrown into a tranquil pond. Maternal exposure during gestation and lactation has been associated with impaired testicular development, diminished sperm counts, and oxidative cerebral damage in progeny [126]. These particles can traverse biological barriers, including the placenta, and can even be transmitted through breast milk, highlighting their extensive distribution. Modified signaling pathways, such as Wnt/β-Catenin and NLRP3/Caspase-1, elucidate how these particles might disrupt embryonic development and growth, impacting both the current and subsequent generations [127], [128]. The hazard transcends reproduction, into the domain of cancer progression. MNPs, akin to covert disruptors, modify the tumor microenvironment, facilitating cellular change and tumor proliferation [129]. Polystyrene NPs have been demonstrated to expedite the evolution of epithelial ovarian cancer in animal models by altering gene expression and compromising antioxidant defenses [130]. Their presence in cervical carcinoma samples suggests a troubling possibility that these particles may accelerate cancer progression, potentially affecting treatment outcomes. MNPs exacerbate the toxicity of environmental contaminants [131], [132]. Their engagement with chemicals such as bisphenol A and heavy metals like lead (Pb) generates a toxic mixture that exacerbates oxidative stress and interferes with endocrine pathways [133]. This synergistic effect resembles a storm escalating across tumultuous seas, exacerbating the damage to reproductive and overall health. At the molecular level, MNPs function as disruptors of cellular machinery. They induce oxidative stress by impairing antioxidant pathways such as Nrf2/ARE and activating pro-inflammatory pathways like TLR4/NOX2 and Notch [134], [135]. These effects result in granulosa cell death, uterine fibrosis, and compromised ovarian follicle development. In males, they impair spermatogenesis and hormone production, hence intensifying their detrimental effects. In addition to reproduction, disturbances in pathways such as PI3K-AKT and MAPK heighten apprehensions over the possibility of tumorigenesis and systemic diseases, indicating that these particles are not merely passive pollutants but rather active agents of detriment [136]. The existence of MNPs in human tissues highlights a concerning reality and their capacity to provoke oxidative stress, inflammation, hormonal disruptions, and transgenerational toxicity poses substantial risks to human health. Their impacts are extensive and complex, exacerbated by interactions with environmental contaminants. Confronting this escalating threat necessitates both scientific innovation and immediate actions to preserve human health and shield future generations from its extensive consequences.

4.5. Effects on pulmonary health

Humans are exposed to airborne MNPs in diverse indoor and outdoor settings. Indoor exposure levels are calculated at 24.3 particles/m³, whereas outdoor levels are estimated at 23.5 particles/m³ [137]. Investigations on airborne MNPs exposure and its health ramifications are increasing, revealing apprehensions among many age demographics, particularly preschoolers, adolescents, pregnant women, and adults, who demonstrate the highest levels of exposure. The COVID-19 epidemic has intensified these issues, as disposable masks composed of plastic-based nonwoven materials can emit MNPs if not disposed of correctly. Reusable masks exhibit an increased likelihood of MNP leakage, presenting environmental and health hazards [138]. Airborne MNPs exposure also transpires through individual habits, occupational settings, and residential situations. Research indicates increased MNP concentrations in BALF of smokers and nasal lavage fluid of office workers relative to couriers [139], [140]. Employees in footwear manufacturing facilities were discovered to possess fibrous airborne MNPs associated with respiratory ailments [141].

Environmental factors, including industrial activity, climate, and population density, affect airborne MNPs availability in various places, presenting health dangers to local populations. Particles of reduced size are more prone to infiltrate the lungs more profoundly, with those measuring less than 1 μm potentially inflicting irreversible harm, whereas particles less than 0.5 μm can access the circulatory and lymphatic systems [142], [143]. Upon inhalation, airborne MNPs may translocate inside the body, potentially traversing the alveolar barrier into the bloodstream and accessing organs such as the thymus [144], [145]. The toxicity of airborne MNPs is affected by parameters including size, shape, and surface charge. Smaller, fibrous MNPs exhibiting cationic characteristics generally demonstrate heightened toxic effects, whereas environmental influences such as UV radiation can modify their properties, hence increasing toxicity. Photoaged MNPs demonstrate heightened biological reactivity, leading to oxidative stress and reduced cell viability [145]. These particles are strongly linked to respiratory conditions like asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (Fig. 6e). In asthma models, MNP exposure enhances macrophage aggregation and mucus production [146]. MNPs can impair lung function in COPD by inducing protease-antiprotease imbalance, mitochondrial malfunction, and cell death via ferroptosis [147]. The presence of airborne MNPs may modify lung flora, thereby heightening vulnerability to respiratory illnesses. Research has shown that MNPs disrupt lung surfactants, resulting in biophysical impairment and exacerbating lung injury. Moreover, airborne MNPs are carcinogenic, presumably owing to their endocrine-disrupting properties [148]. Animal models demonstrate that exposure to forms of MNPs, including polystyrene and polyvinylchloride, elevates oxidative stress, diminishes lung function, and induces systemic inflammation. The deleterious pathways of airborne MNPs encompass metabolic disturbances, genetic toxicity, and lysosomal impairment [149]. The oral use of polystyrene NPs has been associated with hematological impairment and disturbances in lipid metabolism. Moreover, MNPs have demonstrated an impact on macrophage differentiation and lipid buildup, resulting in lysosomal injury [150]. Prolonged inhalation of airborne MNPs may also lead to lung cancer and immune system dysfunction. Although extensive study has concentrated on aquatic and marine creatures, the effects of airborne MNPs on mammals are insufficiently explored, warranting additional investigation into their possible health implications and toxicity pathways.

4.6. Cardiovascular system

Once in the bloodstream, MNPs traverse endothelial barriers, accumulating in cardiovascular tissues such as vascular smooth muscle and the pericardium (Fig. 6f). Animal studies highlight cardiovascular consequences of polystyrene MNP exposure (Fig. 6g), including cardiac fibrosis, myocardial inflammation, apoptosis, and electrical synchronization disturbances mediated by pathways like Wnt/β-catenin and NLRP3/caspase-1 [151], [152].

At the microvascular level, MNPs induce inflammation and pro-thrombotic events marked by elevated interleukin-1β and intercellular adhesion molecules [153]. Prolonged exposure triggers systemic inflammation, impacts perivascular adipose tissue, and disrupts gut flora, contributing to weight gain and chronic inflammatory conditions. Arterial damage, characterized by stiffness, plaque accumulation, foam cell proliferation, and disturbances in lipid metabolism, leads to thicker arterial walls and progressive cardiovascular dysfunction [154]. MNP exposure affects heart function by diminishing inotropic capacity, as evidenced in zebrafish studies [155]. Cellular effects include membrane damage, lysosomal aggregation, and lipid droplet formation precursors to foam cells implicated in atherosclerosis [156]. MNPs disrupt DNA transcription, protein synthesis, and mitochondrial function, provoking oxidative stress via ROS generation. This oxidative stress is accompanied by decreased antioxidants, such as superoxide dismutase, glutathione peroxidase, and catalase [157]. Inflammation mechanisms, including the Th1/Th2 pathway, NLRP3-GSDMD-NFκB axis, and TGFβ1/Smad pathway, lead to elevated cytokines like TNF-α, IL-6, IL-1β, and IL-8. Cellular impacts extend to autophagy, apoptosis, and endoplasmic reticulum stress, causing structural and functional cardiovascular damage. Endothelial senescence exacerbates inflammation, offering potential therapeutic targets, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which show cardioprotective effects [158], [159], [160], [161].

Biomarkers of cardiac injury, including creatine kinase-MB, lactate dehydrogenase, cardiac troponins, aspartate aminotransferase, and N-terminal pro-B-type natriuretic peptide, are elevated following MNP exposure. Vascular toxicity in zebrafish embryos, marked by reduced enhanced green fluorescent protein levels, underscores adverse effects on vascular development. MNPs promote platelet aggregation, hemolysis, and immunological activation, with positively charged particles demonstrating heightened toxicity [162], [163], [164], [165].

However, many findings derive from unrealistic MNP dosages or forms, limiting direct relevance to human health. These observations underscore the complex interplay of oxidative stress, inflammation, and molecular dysregulation contributing to MNP-induced cardiovascular harm.

4.7. Cognitive defects

Humans are exposed to MNPs through everyday items such as textiles, car tires, and packaging, leading to widespread environmental contamination. Research indicates that, unlike larger particles, the blood-brain barrier (BBB) generally protects the brain, polystyrene NPs with size 0.293 µm can cross into the brain within 2 h. The particle’s coating, or biomolecular corona, influences their BBB permeability; cholesterol facilitates their entry, while proteins inhibit it [166].

The presence of plastic nanoparticles in aquatic environments poses additional risks. Positively charged polystyrene NPs with size of 52 nm are toxic to aquatic organisms like Daphnia and alter fish behavior. Smaller nanoparticles notably impact fish, increasing their feeding rates and activity. These particles accumulate in fish brain tissue, crossing the BBB and causing behavioral changes linked to structural brain alterations, raising concerns about long-term health effects on humans [167]. Emerging research reveals that NPs can negatively affect brain health by interacting with α-synuclein protein, which is involved in neurodegenerative diseases such as Parkinson's. NPs promote the formation and spread of α-synuclein fibrils, impair lysosomal function, and accelerate the spread of neurodegenerative pathology, especially in dopaminergic neurons [168].

An in vitro study on polystyrene NPs in brain cells revealed that microglia, the brain's immune cells, took up significantly more polystyrene NPs than neurons or astrocytes (Fig. 6h). This high exposure activated microglia, altering their gene expression, and potentially contributing to cognitive deficits. These findings raise concerns about the impact of NPs on brain health [169]. In studies using the C57BL/6J mouse model, exposure to fluorescently labeled polystyrene MPs over three weeks led to behavioral changes and alterations in immune markers in the liver and brain, with age-dependent effects. Polystyrene MPs accumulated in the brain, induced anxiety-like behavior, and activated microglia, leading to inflammation through the NF-κB signaling pathway. HRAS was identified as a key mediator in this process, with its reduction alleviating inflammation in microglia cells [170]. Additionally, exposure to PLA and PLA-PBAT nanoparticles caused significant acute and sub-chronic toxicity in zebrafish. Short-term exposure to PLA-PBAT showed high toxicity, while long-term exposure resulted in reduced growth, altered behavior, and increased mortality. Behavioral changes included slower swimming, anxiety-like responses, and avoidance behaviors. Disruptions in immune-related pathways were noted, suggesting that PLA-PBAT affects immune regulation and contributes to behavioral abnormalities [171]. In addition, polyethylene terephthalate MNPs increase the percentage of galanin-positive neurons, which regulate pain and appetite, while reducing neurons positive for CART, VAChT, and VIP, affecting feeding, neurotransmitter release, and immune responses in the intestinal nervous system [172].

Like other organs, neurotoxicity is similarly concerning, as MNPs can cross the blood-brain barrier, causing neuroinflammation and cognitive deficits that may exacerbate neurodegenerative conditions. The idea that particles designed for durability in packaging could lead to devastating health consequences underscores the pressing need for innovative solutions to this silent crisis. This comprehensive overview highlights the critical need for further research into MNP’s long-term health impacts to better understand and mitigate their systemic toxicity.

4.8. Endocrine system

MNPs have emerged as silent but significant environmental hazards, intricately tied to endocrine-disrupting chemicals (EDCs) such as bisphenol A, phthalates, Polybrominated Diphenyl Ethers, and organotin. These seemingly invisible agents disrupt critical biological systems, leading to thyroid dysfunction, reproductive anomalies, neurotoxicity, and metabolic disorders. The interplay between MNPs and EDCs represents a complex challenge, requiring deep investigation and innovative mitigation strategies.

MNPs and EDCs impair thyroid function by disrupting the hypothalamic-pituitary-thyroid axis. For instance, bisphenol A and phthalates hinder thyroid hormone receptor binding, alter gene expression, and suppress hormone production, cascading into developmental anomalies and metabolic disorders [173]. Polystyrene MNPs exacerbate these effects, contributing to obesity, precocious puberty, and insulin resistance [174]. These findings suggest that MNPs, often considered a localized pollutant, may have far-reaching impacts on systemic health. It is sobering to consider how these invisible particles can infiltrate intricate hormonal pathways, reshaping the body's regulatory landscape [175]. Zhou et al., explored the toxic effects of polystyrene MNPs on the ocular surface. In vitro, 50 nm and 2 μm polystyrene MP exposure reduced cell viability, induced oxidative stress, and triggered apoptosis. In mice, polystyrene MPs accumulated in the conjunctival sac, reduced goblet cell numbers by up to 60 %, and caused dry eye-like damage, inflammation, and conjunctival dysfunction. These findings reveal the potential of MPs to impair ocular surface health, highlighting the need for further research [176].

The hypothalamic-pituitary-gonadal axis, vital for reproductive health, is similarly vulnerable. MNPs and EDCs disrupt critical hormones like gonadotropin-releasing hormone, follicle-stimulating hormone, and kisspeptin, leading to reproductive disorders and infertility [177], [178]. MNPs also reduce hypothalamic kisspeptin levels, further destabilizing the hypothalamic-pituitary-gonadal axis. These disruptions are particularly alarming, as they suggest that MNPs may not only threaten individual fertility but also pose long-term generational risks. When combined with EDCs, the threat becomes a compounded assault on reproductive functionality [179], [180].

The hypothalamic-pituitary-adrenal axis, which governs stress responses, is yet another victim of MNP interference. Studies on zebrafish reveal that polystyrene NPs elevate cortisol levels, disrupt glucose homeostasis, and induce behavioral changes [181]. Meanwhile, bisphenol A increases adrenal gland mass and alters steroidogenesis, contributing to stress-related illnesses like anxiety, Post-Traumatic Stress Disorder, and metabolic syndromes [182]. Adding to this mix are heavy metals like mercury and cadmium in MPs, which amplify these effects. The idea that tiny plastic particles can disrupt the delicate hormonal balance governing stress and adaptation highlights the pressing need to address their growing prevalence [183].

The reproductive health impacts of MNPs are perhaps among the most disconcerting. In males, MNPs accumulate in reproductive organs, reducing testosterone levels, damaging sperm quality, and triggering oxidative stress and DNA damage. The blood-testis barrier and spermatogenesis are particularly vulnerable, with MPs and EDCs like bisphenol A exacerbating the damage [184], [185]. These findings not only point to individual health risks but also raise societal concerns about declining fertility rates in regions heavily exposed to plastic pollution.

In females, the story is equally troubling. MNPs impair granulosa cells in the ovaries, disrupt folliculogenesis, and alter hormonal balance, leading to conditions like polycystic ovarian syndrome [186]. They also activate the Wnt/β-catenin pathway, causing ovarian fibrosis and reducing ovarian reserve. Compounding this issue, MNPs traverse the placenta, potentially affecting fetal development and leading to developmental anomalies in offspring. The multigenerational effects of these disruptions paint a grim picture of the long-term impact of MNPs on reproductive health and human population dynamics [187], [188].

Aquatic organisms offer a stark lens through which to observe the impact of MNPs. MPs impair ovarian development, reduce reproductive potential, and alter behavior in fish, with cross-generational effects. These findings remind us that the ecological footprint of MNPs extends far beyond human health, threatening entire ecosystems and their interconnected species. The bioaccumulation of MNPs in aquatic species also poses a significant risk to food security, as these contaminants may eventually make their way up the food chain. MNPs and their associated EDCs represent an underappreciated yet critical threat to endocrine and reproductive health. The intricate ways in which these pollutants infiltrate and disrupt biological systems highlight the urgent need for research and mitigation strategies. It is essential to move beyond viewing plastics as mere waste and recognize their role as pervasive agents of systemic toxicity. Acknowledging this reality is the first step toward addressing one of the most pressing environmental and health challenges of our time.

5. Discussion

The pollution caused by MNPs has emerged as a significant environmental and public health concern, with increasing evidence indicating its detrimental impacts on human health. These particles can accumulate in ecosystems and infiltrate the human body via multiple pathways, resulting in considerable health risks. The gastrointestinal tract is a principal site for the deposition of MNPs, which compromise the intestinal barrier and may lead to changes in gut microbiota, oxidative stress, and inflammation. This disruption may lead to metabolic abnormalities, inflammatory illnesses, and chronic diseases, including inflammatory bowel disease. Moreover, accumulating evidence associates MNP exposure with an elevated risk of colorectal cancer, particularly in younger demographics, necessitating further research.

MNPs have been detected in the bloodstream, resulting in possible systemic effects beyond the gastrointestinal tract. These particles can affect multiple organs, such as the liver and kidneys, resulting in inflammation, oxidative stress, and metabolic disruptions. The liver-gut axis is crucial for comprehending how MNPs may worsen liver disease development, highlighting the necessity for study into the role of gut microbiota and its metabolites in liver health. In the kidneys, while several studies indicate possible adverse effects, additional clinical research is necessary to comprehensively elucidate the influence of MNPs on renal illness.

Moreover, MNPs possess the capability to traverse the blood-brain and placental barriers, eliciting apprehensions regarding their impact on neurological health, especially in susceptible populations. The capacity of MNPs to influence neurological illnesses, encompassing cognitive and developmental repercussions, underscores the necessity for further research on the biotoxicity of various MNP kinds. The inhalation of airborne MNPs presents an additional route of exposure, raising concerns regarding respiratory health, especially in illnesses like asthma and COPD. The economic burden of MNPs pollution, together with their capacity to transport additional environmental contaminants, complicates the public health issue further. While MNPs are recognized for their accumulation in cardiovascular tissues, additional study is required to confirm a clear causal link between MNPs and cardiovascular diseases.

The extensive array of possible health effects associated with MNPs exposure highlights the necessity for additional research in this domain. The processes by which MNPs influence many organ systems ranging from the gastrointestinal tract and liver to the brain and kidneys are inadequately comprehended, necessitating further investigation to elucidate the extent of their effects. Multidisciplinary research methodologies are essential to bridge these gaps and formulate solutions for the detection, mitigation, and treatment of health concerns associated with MNPs. Considering the rising production and consumption of plastics worldwide, it is imperative that both scientific communities and politicians focus the health ramifications of microplastic pollution.

6. Conclusion

In summary, the health hazards associated with MNPs are an increasing concern due to their capacity to collect in diverse organs and interfere with biological processes. The gastrointestinal, hepatic, renal, and neurological systems are especially susceptible to damage generated by MNPs, with increasing evidence associating MNPs with metabolic disorders, inflammatory diseases, and cancer. Despite considerable advancements in comprehending the effects of MNPs, numerous uncertainties persist concerning their methods of action and systemic implications. Collaborative multidisciplinary research among scientists and policymakers is crucial for formulating effective solutions to decrease the dangers of MNP pollution and protect public health.

Abbreviation

Muc1 and Muc2- mucin glycoproteins involved in epithelial protection and mucus barrier formation; Klf4- Transcription factor that regulates gene expression; ZO-1- Zonula Occludens-1 tight junction protein occur on endothelial cells; IL-1α, IL-1β, and IL-6 - pro-inflammatory cytokines involved in immune responses; NF-κB- Nuclear Factor kappa-light-chain-enhancer of activated B cells; NLRP3- NOD-like receptor family pyrin domain containing 3; CFTR- Cystic Fibrosis Transmembrane Conductance Regulator; NKCC1- Sodium-Potassium-Chloride Cotransporter 1; LC3II/I and p62 - commonly used as indicators to assess the status of autophagy in cells; RIPK1- Receptor-interacting protein kinase 1; MLKL- Mixed lineage kinase domain-like protein; ALD- alcoholic liver disease; NAFLD- non-alcoholic fatty liver disease; LPS- lipopolysaccharides; TG- triglyceride; TBA- bile acid metabolism; MAPK- Mitogen-activated protein kinase; JNK1/2/3 - c-Jun N-terminal kinases 1, 2, and 3; Nrf2- Nuclear factor erythroid 2-related factor 2; ARE- Antioxidant Response Element; NOX2- NADPH oxidase 2; PI3K- Phosphoinositide 3-kinase; AKT- Protein Kinase B; BALF- Bronchoalveolar Lavage Fluid; COPD- Chronic obstructive pulmonary disease; Th1/Th2- Helper T cells; GSDMD- Gasdermin D, a protein involved in pyroptosis; NFκB- transcription factor involved in inflammation; TGFβ1- Transforming Growth Factor Beta 1; SGLT-2- sodium-glucose cotransporter-2; BBB- blood-brain barrier; HRAS- Harvey Rat Sarcoma Viral Oncogene Homolog; PLA- Poly-Lactic Acid; PBAT- Poly (butylene adipate-co-terephthalate); CART- Cocaine- and Amphetamine-Regulated Transcript; VAChT- Vesicular Acetylcholine Transporter; VIP- Vasoactive Intestinal Peptide; EDCs- Endocrine-disrupting chemicals.

CRediT authorship contribution statement

Divya Arulraj: Writing – review & editing, Writing – original draft, Visualization, Validation. Tapan Kumar Mistri: Visualization, Validation, Supervision, Investigation. John Dennis: Writing – review & editing, Writing – original draft, Methodology.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Dr. L.H. Lash

Data availability

No data was used for the research described in the article.